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Neuromuscular junction

Definition

The neuromuscular junction is a specialized synapse between motor neurons and the muscle fibre they innervate. In vertebrates, the postsynaptic side is referred to as the endplate and contains a high-density of cholinergic receptors that facilitate synaptic transmission.

Latest Research and Reviews

The characteristic muscle weakness in myasthenia gravis (MG) is caused by antibodies against target molecules the neuromuscular junction. Here, Nils Gilhus and colleagues review how these antibodies and other biomarkers can be used to guide MG subgroup classification and treatment, as well as the best tests to detect these antibodies. Moreover, they discuss how the various antibodies are involved in MG pathogenesis.

Mutations in the protein LRRK2 have been associated with Parkinson's disease but little is still known about the basic functions of the protein in the brain. Here the authors show that in fruit flies, LRRK2 regulates retrograde homeostatic synaptic compensation at the larval neuromuscular junction.

Autoantibodies against neuromuscular junction targets are a well-established cause of myasthenic syndromes, and autoantibodies against CNS targets have also been associated with disease. In this Review, Vincent and colleagues discuss key examples of such autoantibodies, and the mechanisms by which they lead to neurological dysfunction.

The mechanism by which FUS mutations cause familial ALS remains unclear. Here, the authors use mouse transgenic models to show that a toxic gain-of-function underlies motor neuron degeneration, and that the toxicity of mutant FUS does not depend on a loss or excess of FUS activity.

The formation and maturation of the neuromuscular junction require the concerted efforts of the presynaptic nerve terminal, the postsynaptic muscle fibre and perisynaptic Schwann cells. In this Review, Robitaille and colleagues describe the molecular and activity-dependent processes that underlie the development of neuron–muscle contacts.

Lrp4 acts bidirectionally and coordinates synapse formation by binding agrin, activating MuSK and stimulating postsynaptic differentiation, and functioning in turn as a muscle-derived retrograde signal that is necessary and sufficient for presynaptic differentiation.